Drug Safety Alerts

Olanzapine MedWatch

05/10/2016


On May 10, 2016, the United States Food and Drug Administration (FDA) issued a MedWatch warning that the antipsychotic medicine olanzapine can cause a rare but serious skin reaction that can progress to affect other parts of the body. FDA is adding a new warning to the drug labels for all olanzapine-containing products that describes this severe condition known as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).

Olanzapine is an antipsychotic medicine used to treat mental health disorders schizophrenia and bipolar disorder. It can decrease hallucinations, in which people hear or see things that do not exist, and other psychotic symptoms such as disorganized thinking. Olanzapine is available under the brand names Zyprexa^®, Zyprexa^® Zydis^®, Zyprexa Relprevv^®, and Symbyax^®, and also as generics.

A search of the FDA Adverse Event Reporting System (FAERS) database identified 23 cases of DRESS reported with olanzapine worldwide since 1996, when the first olanzapine-containing product was approved. FAERS includes only reports submitted to FDA, so there are likely to be additional cases about which FDA is unaware. One patient taking olanzapine experienced DRESS and died; however, this patient was taking multiple medicines that could also have contributed to death (see the Data Summary section of the Drug Safety Communication for more information).

DRESS may start as a rash that can spread to all parts of the body. It can include fever and swollen lymph nodes and a swollen face. It causes a higher-than-normal number of infection-fighting white blood cells called eosinophils that can cause inflammation, or swelling. DRESS can result in injury to organs including the liver, kidneys, lungs, heart, or pancreas, and can lead to death. DRESS is a potentially fatal drug reaction with a mortality rate of up to 10%.

The FDA has provided the following information for health care providers:

• Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), a rare and severe skin reaction accompanied by eosinophilia and systemic signs and symptoms, has been reported in patients treated with drugs that contain olanzapine.  Patients may develop fever with rash and lymphadenopathy. Features of DRESS can also include hepatitis, myocarditis, pericarditis, nephritis, pancreatitis, and pneumonitis.

• A new warning to describe DRESS will be added to the labels of all olanzapine-containing drugs.

• When prescribing olanzapine, inform patients about the risk of DRESS, a severe skin reaction that can occur with treatment.

• Explain the signs and symptoms of DRESS to your patients and tell them when to seek immediate medical care if signs and symptoms occur.

• DRESS consists of three or more of the following:

• Cutaneous reaction (such as rash or exfoliative dermatitis)

• Eosinophilia

• Fever

• Lymphadenopathy

• One or more systemic complications such as hepatitis, myocarditis, pericarditis, pancreatitis, nephritis, and pneumonitis

• If DRESS is suspected, discontinue olanzapine treatment immediately.

• DRESS is a potentially fatal drug reaction with a mortality rate of up to 10%. The pathogenesis of DRESS is unclear; however, it is thought to be the result of a combination of genetic and immunologic factors, such as detoxification defects in the drug metabolism pathway, resulting in toxic metabolite formation and an immune response. Reactivation of viral infections (herpes virus [HHV-6 or HHV-7]) or Epstein-Barr virus (EBV) may also play a role by inducing or amplifying the immune reaction.

• There is currently no specific treatment for DRESS. The important ways to manage DRESS are early recognition of the syndrome, discontinuation of the offending agent as soon as possible, and supportive care.  Treatment with systemic corticosteroids should be considered in cases with extensive organ involvement.

• Report adverse events involving olanzapine (Zyprexa®, Zyprexa Zydis®, Zyprexa Relprevv®, and Symbyax®, and generics), or other medicines to the FDA MedWatch program.

CVS/caremark Response: Please note: There have been no recalls issued on these products. CVS Caremark will continue to dispense these products.

For more information about this issue, health care providers may contact the FDA consumer inquiry line at 1-888-INFO-FDA (1-888-463-6332) or visit https://www.fda.gov/Safety.